PB2412: OUTCOMES OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS–SINGLE CENTRE EXPERIENCE FROM PAKISTAN
Authors: Mussawair Hussain, Tariq Azam, Tariq Ghafoor, Fayyaz Hussain
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disorder of the immune system characterized by excessive activation of macrophages and T cells, resulting in the release of inflammatory cytokines and the destruction of normal tissue comprising familial/genetic HLH (FHL) and secondary HLH. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for HLH, but it is associated with significant morbidity and mortality. Aims: The objective of our study was to determine the outcome of Hemopoietic stem cell transplant in primary HLH in terms of survival, and early post-transplant complications Methods: After obtaining informed consent and approval from ethical committee medical records of 17 patients with primary HLH who underwent HSCT were scanned thoroughly. The data was analyzed using SPSS v26.0 for variables affecting the outcome in terms of overall survival (OS) and early post transplant complications. Patient included in study were those aged 8 years or less and underwent HSCT after 2009. Older patients, patients with incomplete records and cases of secondary HLH were excluded Results: Median age at diagnosis and transplant was 11 months (2 months - 8 yrs) and 2 yrs (4 months – 8 yrs), respectively. Median duration between diagnosis and transplant was 6 months (2 months – 2 yrs). There were 13 (76.5%) male and 4 (23.5%) female patients. All the patient fulfilled HLH 2004 criteria for diagnosis. Transaminitis (ALT ≥ 2 times) before transplant was noted in 76% (n=13) patients. Six (35%) patients had Griscelli syndrome. Genetic diagnosis was available for 2 patients (1 STX1, 1 PRF). The rest (53%, n=9) had no syndromic features and no genetic testing was available. All patients underwent related donor transplant with bone marrow harvest (BMH) as stem cell source. Fourteen (82.4%) were fully HLA matched while 3 (17.6%) were haploidentical with donor being sibling in 70% (n=12) and parent in 30% (n=5). Conditioning regiment was reduced intensity (RIC) in 82%.4 (n=14) and myeloablatvie (MAC) in 17.6% (n=3). Mean CD34 dose was 11.1 x 106/kg (SD ± 9.95), while mean TNC dose was 6.02 x 108/kg (SD ± 3.23). All patients achieved neutrophil engraftment (median day +14) and 94%(n=16) achieved platelet engraftment (median day +26). Donor chimerism at 3 months post-transplant was available for 15/17 patients. 80% (n=12) had complete chimerism while 20% (n=3) had mixed chimerism. Febrile neutropenia (94%),CSA induced HTN (47%), acute GvHD (41%), mucositis (41%) and CMV reactivation (23.5%) were common early post transplant complications. At a median follow up of 5.3 years, OS & DFS were 70.6% (n=12). Cause of death in the 5 patients was Secondary GF followed by infection (2/5), disease relapse (1/5), severe GvHD (1/5), sudden unexplained death (1/5). There was a trend towards better OS in patients with GS (83% vs 63% in non-syndromic, p=0.66) and patients with duration between diagnosis and transplant ≤ 6months (88% vs 50%, p=0.13). However, statistical significance could not be established. OS was significantly superior with sibling donor compared to parent donor (91.7% vs 20%, p=0.01). Summary/Conclusion: Our study demonstrated 70% 5-year overall survival in primary HLH when transplanted with matched related donor. OS was significantly superior with sibling donor compared to parent donor.There was a trend towards favourable outcome with transplant performed within 6 months of diagnosis within continuation phase of treatment, in cases of Griscelli syndrome, and using reduced intensity conditioning. Statistical significance, however, could not be established due to small sample size. Keywords: Allogeneic hematopoietic stem cell transplant, Survival, Hemophagocytic Lymphohistiocytosis (HLH)